Outcomes of liver transplantation in patients 70 years or older: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The rate of liver transplantation is increasing among the elderly population; however, data is limited on the post-liver transplantation outcomes in patients ≥70 years. Given the scarcity in liver allograft resources, a meta-analysis on the outcomes of liver transplantation in patients ≥70 years is warranted. MATERIALS AND METHODS: Multiple databases were searched through March 2022 for studies that reported on the outcomes of liver-transplantation in patients ≥70 years. Meta-analysis was conducted using the random-effects model and heterogeneity was assessed using the I2 statistics. RESULTS: Ten studies were included that analyzed 162,725 patients. The pooled rate of 1-year, 3-years and 5-years post liver transplant survival for patients ≥70 years was 78.7% (72.6-83.7; I2=74%), 61.2% (52.3-69.5; I2=87%), and 48.9% (39.3-58.6; I2=96%), respectively. The corresponding 1-year, 3-years and 5-years survival for patients <70 years were 86.6% (82.4-89.9; I2=99%), 73.2% (63-81.3; I2=99%), and 70.1% (66.8-73.2; I2=99%); respectively. Descriptive p-values of comparison were statistically significant at 1-year and 5-years (p = 0.02 and <0.001). The pooled rate of perioperative complications in patients ≥70 years was 40.7% (26.2-57; I2=93%). The pooled rate of graft failure in patients ≥70 years was 6.7% (3.3-13.1; I2=93%) and in patients <70 years was 3.7% (1-12.4; I2=99%). The pooled rate of perioperative mortality in patients ≥70 years was 16.6% (7.6-32.5; I2=99%) and in patients <70 years was 0.8% (0-33.1; I2=88%). CONCLUSION: Patients ≥70 years undergoing liver transplantation seem to demonstrate significantly lower 1-year and 5-year survival rates as compared to patients <70 years, albeit limited by heterogeneity.

Constrictive pericarditis in the setting of repeated chest trauma in a mixed martial arts fighter.

BACKGROUND: Constrictive pericarditis (CP) is characterized by scarring and loss of elasticity of the pericardium. This case demonstrates that mixed martial arts (MMA) is a previously unrecognized risk factor for CP, diagnosis of which is supported by cardiac imaging, right and left heart catheterization, and histological findings of dense fibrous tissue without chronic inflammation. CASE PRESENTATION: A 47-year-old Caucasian male former mixed martial arts (MMA) fighter from the Western United States presented to liver clinic for elevated liver injury tests (LIT) and a 35-pound weight loss with associated diarrhea, lower extremity edema, dyspnea on exertion, and worsening fatigue over a period of 6 months. Past medical history includes concussion, right bundle branch block, migraine headache, hypertension, chronic pain related to musculoskeletal injuries and fractures secondary to MMA competition. Involvement in MMA was extensive with an 8-year history of professional MMA competition and 13-year history of MMA fighting with recurrent trauma to the chest wall. The patient also reported a 20-year history of performance enhancing drugs including testosterone. Physical exam was notable for elevated jugular venous pressure, hepatomegaly, and trace peripheral edema. An extensive workup was performed including laboratory studies, abdominal computerized tomography, liver biopsy, echocardiogram, and cardiac magnetic resonance imaging. Finally, right and left heart catheterization-the gold standard-confirmed discordance of the right ventricle-left ventricle, consistent with constrictive physiology. Pericardiectomy was performed with histologic evidence of chronic pericarditis. The patient's hospital course was uncomplicated and he returned to NYHA functional class I. CONCLUSIONS: CP can be a sequela of recurrent pericarditis or hemorrhagic effusions and may have a delayed presentation. In cases of recurrent trauma, CP may be managed with pericardiectomy with apparent good outcome. Further studies are warranted to analyze the occurrence of CP in MMA so as to better define the risk in such adults.

A Multicenter Study Into Causes of Severe Acute Liver Injury.

The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often is stated to include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically hepatitis A and hepatitis B), and drug-induced (more specifically, acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a paucity of studies examining the most common causes of acute liver injury (ALI) and those that have been published have been small,2 single-center,2 or examined less severe increases in ALT or AST levels.3,4 We conducted a multicenter study of all patients with an ALT and/or AST level ≥1000 IU/L. Our study had 3 main goals: (1) to determine the most common causes of an ALT and/or AST level ≥1000 IU/L, along with their relative frequencies; (2) to determine differences in etiology based on hospital type (liver transplant center, community hospital, Veterans Affairs hospital); and (3) to confirm or disprove the differential heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen toxicity are the most common etiologies.

Evidence of bias during liver transplant evaluation of non-alcoholic steatohepatitis cirrhosis patients.

BACKGROUND & AIMS: Cardiovascular disease (CVD) is the leading cause of death among non-alcoholic steatohepatitis (NASH) patients and a major source of post-transplant mortality. We sought to examine the effect of comorbidities on listing for orthotopic liver transplant (OLT) in NASH patients. METHODS: In this retrospective cohort study, we included all patients (n = 955) referred to Beth Israel Deaconess Medical Center for OLT between January 2002 and September 2011 and followed their outcomes through March 2018. RESULTS: Compared with non-NASH patients (n = 881), NASH patients (n = 74) were older, more likely female, more overweight, with higher rates of diabetes, hypertension and CVD. NASH patients were less likely to be listed for OLT (55% vs 68.9%, P = 0.01) and were more often declined for 'medical comorbidities' (36.1% vs 15.7%, P < 0.001). However, on multivariate analysis, the only significant predictors of listing were model for end-stage liver disease (MELD) score (OR 1.04, P = 0.01), HCC (OR 2.16, P = 0.01), and diagnosis of non-NASH cirrhosis (OR 2.56, P = 0.003) while controlling for comorbidities. NASH patients declined for OLT died primarily from their liver disease and were not more likely to die from CVD than non-NASH patients. There was no difference in outcomes of NASH vs non-NASH patients on the waitlist and post-transplant. CONCLUSIONS: This study demonstrates potential bias against NASH patients referred for OLT arising from heightened concern for comorbidities. Despite being declined for comorbidities, NASH patients are likely to die of their liver disease.

The Braden Scale, A standard tool for assessing pressure ulcer risk, predicts early outcomes after liver transplantation.

The Braden Scale is a standardized tool to assess pressure ulcer risk that is reported for all hospitalized patients in the United States per requirements of the Center for Medicare and Medicaid Services. Previous data have shown the Braden Scale can predict both frailty and mortality risk in patients with decompensated cirrhosis. Our aim was to evaluate the association of the Braden Scale score with short-term outcomes after liver transplantation (LT). We performed a retrospective cohort study of deceased donor LT recipients at 2 centers and categorized them according to the Braden Scale at hospital admission as low (>18), moderate (16-18), or high risk (<16) for pressure ulcer. We created logistic and Poisson multiple regression models to evaluate the association of Braden Scale category with in-hospital and 90-day mortality, length of stay (LOS), nonambulatory status at discharge, and discharge to a rehabilitation facility. Of 341 patients studied, 213 (62.5%) were low risk, 59 (17.3%) were moderate risk, and 69 (20.2%) were high risk. Moderate- and high-risk patients had a greater likelihood for prolonged LOS, nonambulatory status, and discharge to a rehabilitation facility, as compared with low-risk patients. High-risk patients additionally had increased risk for in-hospital and 90-day mortality after LT. Multiple regression modeling demonstrated that high-risk Braden Scale score was associated with prolonged LOS (IRR, 1.56; 95% confidence interval [CI], 1.47-1.65), nonambulatory status at discharge (odds ratio [OR], 4.15; 95% CI, 1.77-9.71), and discharge to a rehabilitation facility (OR, 5.51; 95% CI, 2.57-11.80). In conclusion, the Braden Scale, which is currently assessed in all hospitalized patients in the United States, independently predicted early disability-related outcomes and greater LOS after LT. Liver Transplantation 23 1153-1160 2017 AASLD.

Vaccination for coronavirus disease 2019 in liver transplantation candidates should be recommended but not mandated.

Content available: Author Interview and Audio Recording.

Outcomes among inpatients with cirrhosis and Clostridioides difficile infection in the modern era: results from an analysis of the National Inpatient Sample.

BACKGROUND: Patients with cirrhosis are at increased risk of Clostridioides difficile infection (CDI). We analyzed outcomes and healthcare utilization in hospitalized cirrhotic patients with CDI. METHODS: The Nationwide Inpatient Sample from 2016-2017 identified 8245 hospitalized patients with a concurrent diagnosis of cirrhosis and CDI. Our primary outcome was in-hospital all-cause mortality. Secondary outcomes were length of stay (LOS), hospitalization charges and costs, shock, sepsis, acute kidney injury (AKI), intensive care unit (ICU) admission, and home discharge. RESULTS: There was no significant difference in all-cause in-hospital mortality between patients with cirrhosis compared to patients without cirrhosis (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 0.89-1.93; P=0.16). Patients with cirrhosis had a slightly but statistically significantly longer mean LOS (+0.57 days, P=0.001). The adjusted difference in mean hospitalization charges was greater in patients with cirrhosis ($+4094, 95%CI $1080-7108; P=0.008), as was the mean hospitalization cost ($+1349, 95%CI $600-2098; P<0.001). There was no difference in the likelihood of sepsis, ICU admission, or home discharge between the groups. Patients with cirrhosis were significantly less likely to develop AKI (aOR 0.82, 95%CI 0.72-0.93; P=0.003). CONCLUSIONS: Mortality outcomes associated with CDI have improved over time. Patients with cirrhosis continue to exhibit greater LOS and hospital costs.

Comparison of transient elastography and Model for End-Stage Liver Disease-sodium to Model for End-Stage Liver Disease-sodium alone to predict mortality and liver transplantation.

OBJECTIVES: Model for End-Stage Liver Disease (MELD) alone and with sodium (MELD-Na) have decreasing predictive capacity as trends in liver disease evolve. We sought to combine transient elastography (TE) with MELD-Na to improve its predictive ability. METHODS: This is a retrospective cohort study comparing the use of TE, MELD-Na, and composite MELD-Na-TE to predict liver transplantation and all-cause mortality, with hepatic decompensation as a secondary outcome. Cox proportional hazards regression was used to measure predictive ability and control for confounders. RESULTS: Of the 214 patients, the mean age was 53 years with 35% being female and 76% being Caucasian. Hepatitis C (59%) and nonalcoholic fatty liver disease (22%) were the most frequent liver disease etiologies. On univariable analysis, MELD-Na [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.2, P < 0.001], TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.13, 95% CI 1.08-1.19, P < 0.001) were associated with death or transplant. On multivariable analysis, MELD-Na was no longer significant (HR 1.08, 95% CI 0.95-1.22, P = 0.27) after adjusting for TE (HR 1.05, 95% CI 1.03-1.07, P < 0.001) while composite MELD-Na-TE remained significant (HR 1.16, 95% CI 1.09-1.24, P < 0.001). Composite MELD-Na-TE predicts mortality or liver transplant with the highest C-statistic of 0.81. Age (HR 1.05, 95% CI 1-1.09, P = 0.04), TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.11, 95% CI 1.06-1.15, P < 0.001) were significantly associated with hepatic decompensation. CONCLUSION: Composite MELD-Na-TE better predicts liver transplantation, death, and hepatic decompensation compared to MELD/MELD-Na or TE alone.

Radiographic and Endoscopic Features of Pancreaticoduodenal Malakoplakia.

Malakoplakia is a rare, granulomatous disorder that is typically triggered by infections in immunocompromised patients. Although it most commonly affects the urinary tract, cases may occasionally occur in the gastrointestinal tract. There are case reports of malakoplakia of the pancreas with associated pathologic description, but none with detailed imaging and endoscopic findings. In addition, description of magnetic resonance imaging characteristics of mass-forming malakoplakia in the literature is sparse. We present a case of pancreaticoduodenal malakoplakia in an immunocompromised patient, including detailed description of magnetic resonance imaging, computed tomography, and endoscopic findings with radiology-pathology correlation. Classic pathologic features of malakoplakia (eg, hypercellularity, inflammation, and mineralization of Michaelis-Gutmann bodies) lead to specific features on imaging, such as marked diffusion restriction, heterogeneous enhancement, calcification, and increased attenuation on nonenhanced computed tomography. These features may help differentiate malakoplakia from other more common lesions that occur in this location, especially if present in an immunocompromised patient.

Acute hepatitis E superinfection leading to chronic hepatitis B reactivation.

Reactivation of chronic hepatitis B (CHB) can be associated with significant morbidity and mortality. There are many different causes of hepatitis B reactivation. This case describes an Asian woman with stable CHB presenting with significant hepatitis flare with markedly elevated serum aminotransferases and hepatitis B virus DNA level. The clinical symptoms were subtle with fatigue and vague right upper quadrant tenderness. We ruled out drug-associated hepatotoxicity and screened for common causes of acute hepatitis. Interestingly, she was noted to have reactive anti-hepatitis E virus (HEV) IgM at initial presentation followed by anti-HEV IgG positivity a month later. The serological pattern confirmed the diagnosis of acute hepatitis E. The combination of antiviral therapy for hepatitis B and resolution of acute hepatitis E resulted in normalisation of serum aminotransferases. This case illustrates the importance of taking a careful history and having a high index of suspicion for various aetiologies when evaluating patients with reactivation of CHB.

Neurologic Manifestations of Hepatitis C Virus Infection.

The extrahepatic manifestations of hepatitis C include effects on the central nervous system, which have been associated with the ability of hepatitis C virus (HCV) to replicate in microglial and endothelial cells and the chronic inflammation induced by HCV. HCV can induce impaired neurocognition, which is clinically manifested by impaired quality of life, fatigue, and brain fog. These cognitive defects can be present even in patients with mild histologic HCV and have been confirmed by neurocognitive testing and brain imaging by magnetic resonance spectroscopy. Neurocognitive defects include loss of functioning memory and subtle changes in attention and processing speed.

Targeting mTOR in Pancreatic Ductal Adenocarcinoma.

Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future.

Computer versus physician identification of gastrointestinal alarm features.

OBJECTIVE: It is important for clinicians to inquire about "alarm features" as it may identify those at risk for organic disease and who require additional diagnostic workup. We developed a computer algorithm called Automated Evaluation of Gastrointestinal Symptoms (AEGIS) that systematically collects patient gastrointestinal (GI) symptoms and alarm features, and then "translates" the information into a history of present illness (HPI). Our study's objective was to compare the number of alarms documented by physicians during usual care vs. that collected by AEGIS. METHODS: We performed a cross-sectional study with a paired sample design among patients visiting adult GI clinics. Participants first received usual care by their physicians and then completed AEGIS. Each individual thus contributed both a physician-documented and computer-generated HPI. Blinded physician reviewers enumerated the positive alarm features (hematochezia, melena, hematemesis, unintentional weight loss, decreased appetite, and fevers) mentioned in each HPI. We compared the number of documented alarms within patient using the Wilcoxon signed-rank test. RESULTS: Seventy-five patients had both physician and AEGIS HPIs. AEGIS identified more patients with positive alarm features compared to physicians (53% vs. 27%; p<.001). AEGIS also documented more positive alarms (median 1, interquartile range [IQR] 0-2) vs. physicians (median 0, IQR 0-1; p<.001). Moreover, clinicians documented only 30% of the positive alarms self-reported by patients through AEGIS. CONCLUSIONS: Physicians documented less than one-third of red flags reported by patients through a computer algorithm. These data indicate that physicians may under report alarm features and that computerized "checklists" could complement standard HPIs to bolster clinical care.